Our long term goal is to maximize the benefits of hyperthermia by developing systems capable of inducing therapeutic thermal doses in entire tumor volumes (to maximize hyperthermic cytotoxicity) and that allow simultaneous delivery of ionizing radiation (to maximize thermal radiosensitization). This application seeks to translate into the radiotherapy clinic a superficial ultrasound hyperthermia system designed for sequential and simultaneous thermoradiotherapy and to evaluate its performance in a human clinical trial. The system (SURLAS for Scanning Ultrasound Reflector Linear Array System) will be based on device developments, numerical modeling and laboratory studies performed under the current funding period. Simultaneous irradiation using electron beams will be tested clinically for the first time. The specific aims are: (1) Develop a SURLAS suitable for superficial sequential/simultaneous thermoradiotherapy clinical trials with human subjects, compatible with electron/photon beam irradiation, and with 3D heating pattern control. Pre-clinical testing is also part of this aim. (2) Develop a Linac-SURLAS-Patient portable interface to minimize the utilization time of the linear accelerator (linac). The goal is to start the hyperthermia treatment outside the linac room; then midway through the heat treatment the patient and the SURLAS are transported into the room and interfaced with the linac. The radiation fraction is then given without interruption of hyperthermia. The final step is to transport the Linac- SURLAS-Patient portable interface out of the linac room to complete the hyperthermia. (3) Develop a practical hyperthermia treatment planning tool to select initial insonation parameter for the SURLAS depending on target volume characteristics, and to assist the physician in evaluating ultrasound isopower contours with respect to radiation isodoses. We will incorporate ultrasound power deposition distributions into treatment planning tools/programs (CT/MRI-based) developed in our department for 3D radiotherapy. And (4), perform a simultaneous hyperthermia and external beam radiation clinical trial with human patients to: (i) Evaluate the thermal performance of the SURLAS against that of the presently used commercial ultrasound hyperthermia system. (ii) Establish quantitatively, using thermal dosimetry indicators, that heating with the SURLAS is better than with the current device. (iii) Demonstrate that the simultaneous administration o hyperthermia and radiation can be more cost effective by permitting the bulk of the patient's hyperthermia to take place outside the linac room. (iv) Establish feasibility of simultaneous hyperthermia and electron beam radiotherapy. This proposal represents the translation of new hyperthermia technology and decades of biological studies into the human clinic. The benefits to patients e.g., greater likelihood of local tumor control outweigh potential risks.